The long-term goal of this research is to better characterize the role of higher-level nervous system connections to brainstem structures involved in speech and in swallowing. The hypothesis to be tested is that there exists an interaction that plays a role in spasmodic dysphonia between the nucleus ambiguus and two major areas of the limbic system, the anterior cingulate cortex and amygdala. Furthermore, we hypothesize these two areas act differentially upon the nucleus ambiguus: the anterior cingulate system is excitatory and acts upon voluntary behaviors, while the amygdalar system is inhibitory and exerts its effect by modulating brainstem reflexes. To test this hypothesis, we propose the following specific aims: 1) to determine the detailed neuroanatomic connection from the nucleus ambiguus to the amygdala and anterior cingulate cortex; 2) to determine the level at which the interaction occurs; and 3) to determine the neurotransmitter receptors involved in the interaction. Each aim builds upon the other, in that the first aim establishes the connection, the second establishes the organization of the connection, and the third characterizes the effect of the connection on its target. Both the monkey and the rat systems will be studied to exploit evolutionary related species differences in brain and brainstem organization. The significance of this research is that, once characterized, these pathways can be targeted for further study with functional imaging studies, for novel medical and surgical therapies, and for the development of physiologic models. It will promote a better understanding of how speech is acquired and generated at the cortical level, of voice disorders such as spasmodic dysphonia, of the focal dystonias, and of speech recovery after brain injury.